TRPV1 Channel‐Mediated Relaxation of Coronary Artery Is Attenuated In Ossabaw Swine with the Metabolic Syndrome

Abstract

TRPV channels are implicated in vascular regulation, but little is known about TRPV1. We tested the hypothesis that coronary smooth muscle and endothelial cell functions are mediated by TRPV1 channels, which contribute to coronary dysfunction in the metabolic syndrome. Coronary arteries were studied from male Ossabaw swine that were lean controls (n = 5) vs. pigs fed excess atherogenic diet for 28 weeks to induce the metabolic syndrome (n = 3). RT-PCR of coronary tissue revealed the TRPV1 isoform mRNA. In freshly isolated cells, fura-2 imaging showed the TRPV1 channel agonist, capsaicin, generated 3-fold greater calcium influx in endothelial vs. smooth muscle. Capsaicin dose-dependently relaxed coronary arterial rings from lean pigs (EC50 = −6.68 ± 0.41 mM), which was attenuated in obese pigs (EC50 = −4.34 ± 1.58 mM). This vasodilation was receptor-mediated, as it was blocked by the antagonist, capsazepine. Nitric oxide synthase inhibition (LNAME, 300 μM), endothelial denudation, and K+ channel antagonists (TEA, 10 mM; IBTX, 10 μM) significantly right shifted relaxation to capsaicin. Patch clamp experiments revealed capsaicin decreased ~70% of outward whole-cell K+ current in smooth muscle. Conclusions: The action of capsaicin on TRPV1 channels to relax coronary conduit artery occurs mainly via endothelial mechanisms and TRPV1 channel signaling is disrupted in the metabolic syndrome. Support: NIH RR013223.